The invention relates to the field of systems, devices and methods for noninvasive or minimally-invasive estimation of cerebrovascular parameters and variables. More particularly, this invention relates to the field of systems, devices, and methods for estimating intracranial pressure (ICP), cerebrovascular resistance, cerebrovascular compliance, and cerebrovascular autoregulation.
Stroke and traumatic brain injury (TBI) rank among the top healthcare challenges faced today. About 800,000 Americans suffer a new or recurrent stroke each year, and strokes take 140,000 lives in the U.S. annually, making stroke the number three cause of death in the U.S., behind only heart disease and cancer [1]. (Reference numerals listed in square brackets in this application refer to citations appearing at the end of the detailed description.) Annually, about 420,000 Americans suffer a traumatic injury to the head, and about 50,000 deaths are attributed to such injuries each year; about 6 million Americans, or 2% of the US population, live with the effects of TBI [2]. Attention to traumatic head injuries has increased recently, as about 15-28% of U.S. soldiers returning from Iraq report some degree of head injury that resulted in either loss of consciousness or altered mental status [3,4]. Recent evidence in animal models suggests that even low-level blast injuries raise ICP and impair cognitive function [5]. This is an important finding, as the majority of service-men and women reporting brain injury suffer from mild traumatic brain injury, in which ICP is currently not monitored [4].
Brain tissue is highly vulnerable to unbalanced oxygen supply and demand. A few seconds of oxygen deficit may trigger neurological symptoms, and sustained oxygen deprivation over a few minutes results in severe and often irreversible brain damage. Normally, brain tissue is protected from injury by its exquisite ability to modulate cerebral blood flow to match oxygen demand, primarily by modulating the resistance of the cerebrovascular bed. This autoregulatory ability, however, can be critically impaired due to brain damage (e.g., stroke or traumatic brain injury), putting such patients at great risk of serious further brain injury. The rapid dynamics coupled to the potential for severe injury necessitates continuous, and ideally non-invasive, cerebrovascular monitoring, at least in the populations at greatest risk for developing brain injury.
Monitoring the cerebrovascular state of a patient, or an animal, suffering from cerebrovascular accident or disease—such as stroke, cerebral hemorrhage, TBI or hydrocephalus—requires assessing the cerebrovascular system's ability to regulate a desired blood supply. Cerebral blood flow depends on arterial blood pressure (ABP) and ICP as well as cerebrovascular parameters, such as cerebrovascular resistance and cerebrovascular compliance. Specifically, the difference of ABP and ICP is termed cerebral perfusion pressure (CPP), and constitutes the driving pressure for cerebral blood flow. As a consequence, monitoring of ICP, cerebrovascular parameters and autoregulation is central to diagnosis, tracking of disease progression, and titration of therapy for a range of conditions involving cerebral pathophysiology.
Monitoring ICP in current clinical practice requires penetration of the skull and insertion of a catheter or pressure sensor into the ventricular or parenchymal space [24]. Thus current methods for monitoring ICP are significantly invasive, and are therefore reserved for only the most severe of cases. Other measurement methods based on lumbar puncture are also used in clinical practice; however, in addition to being invasive, these methods pose a risk of herniation of the brain stem in patients suffering from intracranial hypertension. The invasiveness of current methodologies for the measurement of ICP results in such measurements being taken only in patients at highest risk of developing intracranial hypertension and associated compromised cerebral blood flow. Thus, the current ICP monitoring paradigm excludes a large patient pool that can potentially benefit from such monitoring, such as those suffering from or suspected of suffering from mild traumatic brain injury. Therefore, there is a strong need for noninvasive or minimally-invasive methods and systems for estimating and monitoring ICP and cerebrovascular autoregulation.
Research and development efforts related to noninvasive or minimally-invasive estimation of ICP and autoregulation have been disclosed in the scientific literature and patent descriptions, particularly over the last decade [9-15]. None of these approaches, however, has all of the following desirable features: ability to estimate ICP, hence CPP; ability to estimate cerebrovascular resistance and compliance, thereby permitting an assessment of autoregulation; ability to estimate these variables and parameters continuously, at beat-to-beat temporal resolution, and in real time; minimally or non-invasively; at the patient's bedside; without reference to patient- or population-specific data; ability to exploit fundamental physiological relationships rather than empirical or statistical associations; without the need for any calibration; and at high fidelity.
Furthermore, the portion of the literature addressing cerebrovascular autoregulation has typically been handicapped by the lack of a noninvasive ICP estimate, and has therefore had to substitute ABP for CPP in assessing autoregulation. This presents a serious methodological deficiency for existing indices of autoregulation.
Non-invasive and continuous estimation of ICP will have impact at three levels. First, it will save patients from the associated risks and complications. Second, it will open up the possibility for use in many other scenarios where ICP monitoring would improve care, but is currently avoided because of the highly invasive nature of available methods. For instance, the somewhat arbitrary boundaries that presently distinguish between mild, moderate and severe TBI could perhaps be clarified [8]. Given the brain's sensitivity to even short disruptions in oxygen supply, continuous tracking of ICP and vascular autoregulatory capacity seem indicated for diagnosis and monitoring of mild TBI. Another example might be the monitoring and programming of CSF shunts in chronic hydrocephalus patients. Third, non-invasive ICP estimation could be informative in a still broader population where elevated ICP may be involved in the pathophysiological pathways, possibly even in such common conditions as migraine (where studies indicate a correlation between intracranial hypertension and migraine involving bilateral transverse sinus stenosis [27]) and chronic daily headache [28].